br Materials and methods br Results br Discussion Cells

Materials and methods
Results
Discussion Cells in the human body, especially in the cardiovascular and musculoskeletal systems, undergo a variety of mechanical stimuli. In order to ensure human movement, the strength of stretching muscles acts on cartilage and bone, moving joints through tendons. On the vascular wall, chpg are subjected to continuous fluid shear stress from blood flow, which can regulate the rolling and adhesion of white blood cells. Similarly, during breathing and heart beating, lung and heart tissues are periodically stretched [19]. Cell movement and tissue formation are also affected by the mechanical and structural properties of ECM. For example, the distribution of matrix proteins can affect cardiac arrays during cardiovascular development. Therefore, mechanical clues are important not only in tumor microenvironment but also in normal cell physiology activities. At present, most of the studies on the physiological processes of cells and tissues focus on the biochemical signals that trigger physiological processes, such as changes in molecular structure and signal pathways, and consider that the mechanical properties of cells or tissues are only by-products of their functions [20,21]. However, many organ dysfunction and diseases can be understood as caused by changes in the mechanical properties of related tissues. Our results reveal the key role of LSS in cancer cell proliferation, which contribute to the malignancy of distant tumor metastasis. The interaction of intracellular macromolecules constitutes the intracellular signaling network, which is the basis of cell life activity and function regulations. Cell behaviors are all controlled by various signaling molecules. Mechanical microenvironment is an important regulator of life formation and function. Cells accurately perceive the force spatiotemporally and convert mechanical clues into chemical signals, which produce a series of biological responses. The change of mechanical properties of cells or the defect of force signals can also lead to the occurrence of diseases in organisms [22]. Mechanical signal transduction is a complex cellular communication process involving multiple molecules and signals, which coordinates with each other and ultimately achieves accurate intracellular sensing of extracellular microenvironment. Current studies mainly consider that force signals are transduced in cells through several ways, e.g. the decomposition and reorganization of cytoskeleton after cell sense the force [23], since cytoskeleton can provide signal transduction for many enzymes. The cytoskeleton mechanical transmission is mainly related to cell migration. Myosin and microtubules and other key molecules of cytoskeleton play an important role in cell migration. Apart from cytoskeleton, extracellular matrix and adhesion molecule links extracellular and cellular as a whole in the microenvironment [24]. Focal adhesion kinase (FAK) is a widely expressed protein tyrosine kinase, binds to proteins via Src homology 2 and 3 (SH2 and SH3) [25]. The amino terminal of FAK can bind to integrins then phosphorylated FAK, transfers extracellular cells to intracellular and triggers a series of cellular responses, including ERK phosphorylation. Furthermore, the molecular dynamics mechanism of the signal converted by the ion sensitive channel is also a fast but unclear mechanism of the transmembrane signal communications [26,27]. YAP, as a mechanical receptor in cells, plays an important role in the conversion of mechanical signals to chemical signals [15,28]. It also participates in multiple signaling pathways. YAP is also associated with actin, which plays a role in cell migration and enhances the malignant behavior of cancer cells. YAP is related to many signal molecules, e.g. the classical Hippo pathway. The classical Hippo pathway is the phosphorylation of upstream kinases MST1 (also known as STK4) and MST2 (also known as STK3), which can activate LATS1 and LATS2. Phosphorylated LATS1 and LATS2 inactivate YAP. Phosphorylated YAP resides in the cytoplasm, binds to 14-3-3 protein, and initiates ubiquitination degradation pathway. Although traditional conceptual YAP and TAZ molecules are mostly related to the growth of tissues and organs, YAP and TAZ also play a key role in the occurrence and development of cancer [29,30]. In addition, YAP can also act as a mechanoreceptor molecule in cells to respond to changes in various extracellular mechanical states [15]. Therefore, we explore whether YAP is involved in LSS-induced cell proliferation and the relationship between ERK and YAP. The results showed that ERK/YAP could promote mechanical induced cell proliferation in an upstream-downstream manner.